Phase-separated polymer coatings

ABSTRACT

The present invention includes a drug release system. The drug release system comprises a bulk polymer phase and a polymeric drug-enriched phase within the bulk polymer phase. At least one, drug is incorporated into the drug-enriched phase.

BACKGROUND OF THE INVENTION

The present invention relates to a system for controlled drug releasewithin a vessel lumen, and to a method and to a device for controlleddrug release.

A device for providing a continuous release of drugs over an extendedperiod of time following from a single administration of a drugreleasing material has wide application in treating disease. One type ofcontinuous drug release mechanism is based upon degradation ofbiodegradable polymers. The biodegradable polymers have drugsincorporated within them. As the biodegradable polymers hydrolyze overtime, the drugs are released. Hydroxycarboxylic acid polymers have beenused to release drugs in this manner.

One other modality of drug release is a prolonged, though discontinuousrelease of drugs. Frequently, with a discontinuous release, there is alag phase of no or negligible drug release when a drug delivery deviceis delivered to an in situ site for drug release.

One problem with sustaining drug release is that when drugs,particularly water soluble drugs, are incorporated into polymers, it isdifficult to prevent a rapid, uncontrolled release of the drugs. As usedherein, the term “water soluble drug” is defined as a hydrophiliccompound with a solubility in water greater than 1 percent (w/v) andthat is practically insoluble in nonpolar organic solvents such as ethylacetate, methylene chloride, chloroform, toluene, or hydrocarbons. Thisrapid, uncontrolled release from a drug-polymeric matrix is known as a“burst effect.” The burst effect is particularly troublesome with highdrug loading.

One other type of uncontrolled drug release is characterized by a “lageffect.” The lag effect occurs when the rate of drug release decreasesto a negligible value.

The degree of drug release from a polymeric-drug matrix is, in part,controlled by the morphology of the polymeric-drug matrix. Themorphology is, for some embodiments, a single-phase dispersion and forother embodiments, is a multi-phase dispersion. A single-phasedispersion is typically transparent when viewed in natural light. Thesingle phase dispersion is clear and transparent because both the drugand the polymer have a mutual miscibility. A multi-phase dispersion hasmicro domains that give the dispersion a cloudy appearance. For somemulti-phase dispersions, drugs are embedded in a polymeric matrix asparticles.

Drug release is also controlled by the degree of drug loading. Matricesthat have dispersed drug particles that do not contact each other tendto have a slow release of drug. A drug carrier such as blood istypically required to move the drug through the matrix and into thebloodstream of a living being.

Drug-polymeric matrices have been used to deliver drugs in situ througha vehicle such as a stent. The drug-polymeric matrix has been applied asa coating or a wrap to the stent. U.S. Pat. No. 5,605,696, which issuedFeb. 25, 1997, describes a drug loaded polymeric material that isapplied to an intravascular stent. The drug-polymeric matrix definespores, multilayered to permit a combination of different drugs in asingle stent. The stent also includes a rate controlling membrane thatcontrolled retention and delivery of selected drugs to the affectedblood vessel. The drug is dispersed as small particles, having a maximumcross-sectional dimension of 10 microns.

DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of one embodiment of the drug deliverysystem of the present invention wherein a system component is below thepercolation threshold.

FIG. 2 is a perspective view of one embodiment of the drug deliverysystem of the present invention wherein a system component is above thepercolation threshold.

FIG. 3 a is a perspective view of the drug delivery system of thepresent invention wherein the pore structure is discontinuous.

FIG. 3 b is a perspective view of the drug delivery system of thepresent invention wherein the pore structure is semi-continuous.

FIG. 3 c is a perspective view of another embodiment of the drugdelivery system of the present invention wherein the pore structure iscontinuous.

SUMMARY OF THE INVENTION

One embodiment of the present invention includes a drug release system.The drug release system releases one or more drugs when implanted in ahuman being or other vertebrate but does not display a substantialrelease of drugs when outside of the human being or other vertebrates.The drug release system comprises a bulk polymer phase and a polymericdrug-enriched phase within the bulk polymer phase. The drug releasesystem also includes at least one drug that is incorporated in thepolymeric drug-enriched phase. The drug release system of the presentinvention releases one or more drugs in situ while decreasing the rateof release of the drug when the device is not in situ. The drug profilerelease is predictable and preselectable.

Another embodiment of the present invention includes a coating thatcomprises a drug release system. The drug release system has desirablefilm properties which render it useful as a coating for an implantabledevice. The present invention also includes an implantable device with acoating that is adhered to the implantable device. The coatedimplantable device releases one or more drugs in a predictable andpreselectable manner when implanted in a human being or othervertebrate.

Another embodiment of the present invention includes a method forsubstantially continuously releasing drugs. The method includesattaching or adhering a drug delivery system to an implantable medicaldevice. The drug delivery system comprises a bulk polymer phase and apolymeric drug-enriched phase within the bulk polymer phase. The drugrelease system also includes one or more drugs that are incorporated inthe polymeric drug-enriched phase.

One other embodiment includes a device for continuously and predictablyreleasing drugs. The device comprises a drug release system thatcomprises a bulk polymer phase. The drug release system also includes adrug-enriched polymeric phase within the bulk polymer phase. The drugrelease system also includes at least one drug which is incorporatedinto the polymeric drug-enriched phase wherein the drug-enriched phasecomprises sites within the bulk polymer phase that are continuous inboth cross-section and longitudinal directions. Other embodiments of thedevice include implantable devices, such as a stent, catheter orguidewire, to which the drug release system is attached or adhered.

Another embodiment of the present invention includes a method for makinga device for a continuous release of drugs. The method comprisesproviding a bulk phase polymer and providing a drug that issubstantially insoluble in the bulk phase polymer. The method alsoincludes providing a drug enriched polymer. The drug enriched polymer issubstantially insoluble in the bulk polymer. One or more of the drugsare soluble in the drug-enriched polymer. The method further comprisesproviding a solvent. The bulk phase polymer, the drug enriched polymerand the drug or drugs are blended in the solvent so that the drug ordrugs are incorporated into the drug receiving polymer and the drugenriched polymer is dispersed within the bulk polymer.

DETAILED DESCRIPTION

One embodiment of the present invention includes a drug release systemcomprising two or more polymers that are insoluble in each other. Thepolymers are blended in a solvent to form two polymer phases whichcreate a polymer blend. At least one drug is added to the polymer blend.The drug or drugs are soluble in one of the polymer phases, hereinafterreferred to as the “drug-enriched polymer” or “drug enriched polymerphase.” The polymer blend with the drug enriched polymer phase isremoved from the solvent and is allowed to set. Once set, this drugrelease system has a morphology that has a predictable and preselectabledrug release profile with desirable film properties. The desirable filmproperties include adherence or attachment to a polymeric or metalsurface of an implantable device. Thus, the drug release system serves adual function of predictable, preselectable drug delivery and coating animplantable device.

The term “preselectable” as used herein refers to an ability topreselect one or more drugs to be released. “Preselectable,” for someembodiments, also refers to a rate of drug release.

The polymer phase that includes the soluble drug, the drug-enrichedpolymer phase, preferably has a glass transition temperature, Tg, lessthan human body temperature of about 37 degrees Centigrade. This polymerphase shall be referred to herein as a “drug-enriched polymer.” Uponincorporating one or more drugs into the polymer, the polymer is kept ata temperature that is lower than the glass transition temperature. Theterm “glass transition temperature” as used herein refers to atemperature at which the polymer chain undergoes long range motioncharacterized by a transition from a glassy state to a rubbery state.The glass transition temperature is also the temperature at which therate of diffusion within the polymer phase changes by several orders ofmagnitude as the polymer goes from the glassy state to the rubberystate.

A polymer with a Tg that is less than 37 degrees Centigrade is used asthe drug-enriched polymer because the diffusion rate of molecules, suchas drug molecules within the polymer, decreases one to two orders ofmagnitude when the polymer is exposed to a temperature that is below theTg. The Tg features of the drug enriched polymer impart to the polymerfeatures that allow additional control of the drug delivery rate. Forinstance, when the polymer is at a temperature below its Tg, it will notbe within a living being, such as a human being: At these lowertemperatures, the drug diffusion is suppressed and the drug does notprematurely diffuse through the bulk polymer. This is desirable becauseoutside of a human being, drug diffusion through the polymer isproblematic. Once the drug-enriched polymer phase is implanted, thetemperature of the polymer approaches its Tg and the rate of diffusionof drug through the polymer increases. The drug or drugs are deliverableto a predetermined site, such as to a lesion in a blood vessel. Once atthis site, the drugs diffuse through the drug-enriched polymer. Polymerswhich can be used as the drug enriched phase include polyethylene oxide,PEO, and poly n-vinyl pyrrolidone.

The drug enriched polymer is at a concentration greater than thepercolation threshold concentration, which is about 33-36%, assuming amorphology of spherical domains, to form a continuous drug enrichedphase within the bulk polymer film. The term “percolation threshold” asis used herein refers to a state achieved when an aqueous drug enrichedphase forms a continuous, interconnecting network throughout the bulkpolymer thickness. The continuous drug enriched phase is one where thedrug-enriched polymer phase is substantially uniformly distributedwithin the bulk phase, such as is shown generally, in one perspectiveview, at 10, in FIG. 1.

The-continuous drug-enriched polymer phase, is illustrated at 11 in FIG.1, for one embodiment. The bulk polymer 12 forming the phase which isnot drug-enriched, referred to herein as the “bulk phase” or “bulkmatrix” has acceptable film properties. One suitable polymer for use inthe drug release system, as a bulk phase polymer, ispoly(ethylene-co-vinyl)alcohol, which is also known as EVAL. EVAL is athermoplastic polymer, manufactured by EVAL Company of America (EVALCA),of Lisle, Ill. This polymer 12 has a formulation which is the following:

The drug-enriched polymer containing the drug has, for one embodiment,the formula:

One drug delivery system is composed of two components: one, ahydrophobic component, including but not limited topoly(ethylene-co-vinyl alcohol), and two, a hydrophilic component, whichincludes but is not limited to polyethylene glycol. The dissimilarity ofsolubility parameters of the components results in a phase separation ofthe two polymer phases. The two polymers are blended in a commonsolvent, such as dimethyl sulfoxide or N,N-dimethylacetamide, to forn asolution. At least one therapeutic drug is added to the solution, suchas the therapeutic drug, actinomycin D. However, the therapeutic drug ordrugs are not limited to the antiproliferative class of drugs which haspreferential solubility in the hydrophilic phase.

For some embodiments, the drug delivery system comprising the drug andpolymer solution is applied to an implantable device to form a coatingon the device. The coated device is dried to remove the solvent, byvacuum or by convection processing. The drying allows the polymerswithin the applied solution to form phases and to separate. Once dried,the coating retains flexibility.

If the volume percent of the drug enriched hydrophilic phase is lessthan about 30%, the hydrophilic polymer and drug will exhibit adiscontinuous pore structure, as shown at 10 in FIG. 1. Thediscontinuous pore structure shown in FIG. 1 is defined as being belowthe percolation threshold.

If the volume percent of the drug enriched hydrophilic phase is greaterthan about 30%, the hydrophilic polymer and drug will exhibit a porestructure 22 that is continuous throughout the volume of the bulkpolymer 24, as shown generally at 20 in FIG. 2. The continuous porestructure 22 within the bulk polymer volume of the polymer 24 is definedas being above the percolation threshold.

The elution of the drug from a drug release coating, such as is shown inFIG. 1, below the percolation threshold, is dependent upon the diffusionof the drug within the drug-enriched polymer 11 through the hydrophobicbulk polymer 12. This is contrary to the diffusion of the drug from adrug release coating above the percolation threshold, such as isillustrated in FIG. 2, which is dependent upon the diffusion of the drugfrom the pore network 22, and upon the mean pore length.

Common solvents and co-solvents usable for the blending of the polymersinclude dimethyl sulfoxide, N,N-dimethylacetamide, dimethylsulfoxide-tetrahydrfuran, and isopropanol-water.

Once the polymers are blended and the drug is incorporated in thedrug-enriched polymer, the solvent is evaporated. The evaporation iscarried out, for some embodiments, at a reduced pressure and at atemperature that is as close to ambient temperature as possible.

Examples of such drugs include antiproliferative substances as well asantineoplastic, anti-inflammatory antiplatelet, anticoagulant,antifigrin, antithrombin, antimitotic, antibiotic, antioxidant, andcombinations thereof. A suitable example of an antiproliferativesubstance includes actinomycin D, or derivatives and analogs thereof,manufactured by Sigma-Aldrich 1001 West Saint Paul Avenue, Milwaukee,Wis. 53233; or COSMEGEN available from Merck). Synonyms of actinomycin Dinclude dactinomycin, actinomycin IV, actinomycin I1, actinomycin X1,and actinomycin C1. Examples of suitable antineoplastics includepaclitaxel and docetaxel. Examples of suitable antiplatelets,anticoagulants, antifibrins, and antithrombins, include sodium heparin,low molecular weight heparin, hirudin, argatroban, forskolin,vapisprost, prostacyclin and prostacyclin analogs, dextran,D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole,glycoprotein Iib/IIIa platelet membrane receptor antagonist, recombinanthirudin, thrombin inhibitor, available from Biogen, and 7E-3B, anantiplatelet drug from Centocore. Examples of suitable antimitoticagents include methotrexate, azathioprine, vincristine, vinblastine,antiproliferative agents include angiopeptin (a somatostatin analog fromIbsen), angiotensin converting enzyme inhibitors such as CAPTOPRIL,available from Squibb, CILAZAPRIL, available form Hoffman-LaRoche, orLISINOPRIL, available form Merck, calcium channel blockers such asNifedipine, colchicine, fibroblast growth factor (FGF) antagonists, fishoil, omega 3-fatty acid, histamine antagonists, LOVASTATIN, an inhibitorof AMG-CoA reductase, a cholesterol lowering drug from Merck, acholesterol lowering drug, monoclonal antibodies such as PDGF receptors,nitroprusside, phosphodies terase, inhibitors, prostaglandin inhibitor,Seramin, a PDGF antagonist, serotonin blockers, steroids, thioproteaseinhibitors, triazolopyrimidine, a PDGF antagonist, and nitric oxide.Other therapeutic substances or agents which may be appropriate includealpha-interferon, genetically engineered epithelial cells, anddexamethasone.

In-another embodiment, the drug delivery system comprises a polymer filmdoped with one or more therapeutic drugs. The polymer film is comprisedof a graft copolymer, the copolymer having segments that differsignificantly in their solubility parameters. The solubility differencesresult in phase separation of the two segments. In this embodiment, thehydrophobic polymer is poly(ethylene-co-vinyl alcohol), commerciallyknown as EVAL. In the embodiment, a hydrophilic copolymer such as apolyethylene oxide with a molecular weight between 3200 and 20,000 withan isocyanate functionality is grafted as a side chain, in the followingchemical reaction:

The graft copolymer with a molecular weight of 3200 daltons isfunctionalized with 0.27 mol percent of the hydroxyl functionalities ofthe poly(ethylene-co-vinyl alcohol) and has an average of two ethyleneoxide polymers grafted to the polymer. The total volume fraction ofhydrophilic polymer and drug occupies approximately 35% of the polymermatrix and assumes a cylindrical-like pore morphology. The graftedco-polymer with a molecular weight of 3200 daltons functionalized with0.68 mole percent of the hydroxyl functionalities has an average of fiveco-polymer segments attached to any given polymer chain. The hydrophilicgraft polymer volume containing the polyethylene oxide functionality andthe drug, forming a drug enriched polymer, are present at approximately50 volume percent. The drug enriched polymer assumes a lamellarstructure as is shown at 40 c in FIG. 3 c.

The morphologies of the drug enriched graft polymer 32 within the bulkpolymer substrate 34, are shown at 40 a, 40 b and 40 c, respectively, inFIGS. 3 a, 3 b and 3 c. These different morphologies are due to anincreasing concentration of the drug enriched polymer phase 32 a, 32 band 32 c, respectively, in which one or more drugs is incorporated. Athigher concentrations, the drug enriched polymer phase coalesces to forma lamellar morphology. The drug release embodiment 40 a, shown in FIG. 3a, is a discontinuous pore structure, with the drug-enriched polymerphase 32 a discretely dispersed in the bulk phase 34 a.

The drug-enriched polymer structure 32 b in FIG. 3 b has asemi-continuous phase and in FIG. 3 c, the drug-enriched polymer 32 chas a continuous phase in which the drug is soluble and diffusible fromthe continuous phase, when implanted into a living being. Thesemi-continuous phase 32 b comprises sites that are discrete incross-section but continuous in a longitudinal direction, as is shown inFIG. 3 b. The continuous phase 32 c, shown in FIG. 3 c, defines achannel 33 c in which the drug is diffusible from the bulk polymer 34 cto the polymer interface 35. The drug-enriched sites are continuous inboth cross-section and in a longitudinal direction.

EXAMPLE 1

One exemplary composition that produces the drug release morphology ofFIG. 3 c includes an EVAL polymer with 66 weight percent ethylenegroups, 43.32 weight percent vinyl alcohol functionalities and 0.68weight percent vinyl ether groups. The weight percent refers to thepercent of the total drug release system weight. The vinyl ether groupswere functionalized with PEO-isocyanate, which forms a urethane linkage,using groups that have a molecular weight of a side group of 3200 g/mol.The side groups comprise 33 weight percent of the total EVAL/PEOpolymer. The composition of the PEO-isocyanate blend is 75 weightpercent functionalized EVAL and 25 weight percent drug. This compositiongives rise to a 50 weight percent hard, bulk phase and a 50 weightpercent drug/PEO side chain phase. The final structure is a lamellarstructure.

The chemical reaction is as follows:

(x)=66 weight %; (y)=44 weight %. M is approximately equal to 70 units.Molecular weight is approximately 3200 units. With the drug releasesystem such as is shown at 40 c in FIG. 3 c, drug release issubstantially continuous within a human being.

The drug release system of the present invention is deliverable to atreatment site by attachment to a device such as a stent or catheter orguidewire. For other embodiments, the drug release system isencapsulated and ingested or subcutaneously injected. For otherembodiments, the drug release system is adhered to a prosthetic deviceor a graft or other implantable device by methods known to those skilledin the art.

Once positioned within a living being by one of the implantable devices,the drug release system commences delivering drugs because the polymercomponent of the drug-laden phase is at a temperature below its glasstransition temperature. The release of drugs is substantiallycontinuous.

While specified embodiments of the invention have been herein described,it is to be appreciated that various changes, rearrangements andmodifications may be made therein without departing from the scope ofthe invention as defined by the appended claims.

1-43. (canceled)
 44. a drug-delivery stent comprising a coating, whereinthe coating includes: a first-polymer phase comprising a first-polymer,a second-polymer phase comprising a second-polymer, and a drug; wherein,the second-polymer phase is substantially or completely immiscible inthe first-polymer phase, and the drug is preferentially incorporated inthe second-polymer phase.
 45. The stent of claim 44, wherein thefirst-polymer phase has a film forming property.
 46. The stent of claim44, wherein the drug comprises an antibiotic, antiproliferative,antineoplastic, anti-inflammatory, antiplatelet, anticoagulant,antifibrin, antithrombin, antimitotic, antioxidant, or a combinationthereof.
 47. The stent of claim 44, wherein the second-polymer phasecomprises sites that are substantially or completely disconnected in thecoating, such that elution of the drug from the coating occurs throughtransport of the drug across both the second-polymer phase and thefirst-polymer phase.
 48. The stent of claim 44, wherein thesecond-polymer phase comprises sites that are substantially orcompletely connected in the coating, such that elution of the drug fromthe coating includes transport of the drug primarily through thesecond-polymer phase.
 49. The stent of claim 44, wherein thesecond-polymer phase comprises sites that are substantially orcompletely connected in the coating, such that elution of the drug fromthe coating includes transport of the drug exclusively through thesecond-polymer phase.
 50. The stent of claim 44, wherein theconcentration of the second-polymer phase in the coating is less than orequal to about 30% by volume.
 51. The stent of claim 44, wherein theconcentration of the second-polymer phase in the coating is greater thanor equal to about 30% by volume.
 52. The stent of claim 44, wherein thecoating comprises the second-polymer phase in a concentration that isless than or equal to a percolation threshold of the coating.
 53. Thestent of claim 44, wherein the coating comprises the second-polymerphase in a concentration that is greater than or equal to a percolationthreshold of the coating.
 54. The stent of claim 44, wherein thesecond-polymer phase has a glass-transition temperature of less thanabout 37° C.
 55. The stent of claim 44, wherein the drug has apreferential solubility for the second-polymer phase, such that the drugbecomes preferentially incorporated in the second-polymer phase in thecoating.
 56. The stent of claim 44, wherein the drug has a preferentialsolubility in a solvent used to form the coating, the solventpreferentially solubilizes the second polymer over the first polymer,and the drug becomes preferentially incorporated in the second-polymerphase upon removing the solvent to form the coating.
 57. A method ofcoating a stent comprising incorporating a drug preferentially in asecond-polymer phase during a coating process, wherein the coatingprocess comprises: forming a coating composition comprising a firstpolymer for a first polymer phase, a second polymer for a second polymerphase, a drug, and a solvent; wherein the second polymer issubstantially or completely immiscible in the first polymer; applyingthe composition to a stent; and removing the solvent from thecomposition to form a coating including the first-polymer phase, thesecond-polymer phase, and the drug, wherein the drug is preferentiallyin the second-polymer phase.
 58. The method of claim 57, wherein theincorporating includes selecting a drug with a preferential solubilityin the second-polymer phase, such that the drug becomes preferentiallyincorporated in the second-polymer phase in the coating.
 59. The methodof claim 57, wherein the incorporating includes selecting a drug with apreferential solubility in the solvent, and the solvent preferentiallysolubilizes the second polymer over the first polymer, such that thedrug becomes preferentially incorporated in the second-polymer phaseupon removing the solvent to form the coating.
 60. The method of claim57, wherein the drug comprises an antibiotic, antiproliferative,antineoplastic, anti-inflammatory, antiplatelet, anticoagulant,antifibrin, antithrombin, antimitotic, antioxidant, or a combinationthereof.
 61. The method of claim 57, wherein the second-polymer phasehas a glass-transition temperature of less than about 37° C.
 62. Themethod of claim 57, wherein the coating comprises the second-polymerphase in a concentration that is less than or equal to a percolationthreshold of the coating composition.
 63. The method of claim 57,wherein the coating comprises the second-polymer phase in aconcentration that is greater than or equal to a percolation thresholdof the coating composition.
 64. The method of claim 57, wherein theconcentration of the second-polymer phase in the coating is less than orequal to about 30% by volume.
 65. The method of claim 57, wherein thesecond-polymer phase comprises sites that are substantially orcompletely disconnected throughout the coating, such that elution of thedrug from the second-polymer phase occurs through transport of the drugacross both the second-polymer phase and the first-polymer phase. 66.The method of claim 57, wherein the concentration of the second-polymerphase in the coating is greater than or equal to about 30% by volume.67. The method of claim 57, wherein the second-polymer phase comprisessites that are substantially or completely connected throughout thecoating, such that elution of the drug from the second-polymer phaseincludes transport of the drug primarily through the second-polymerphase.
 68. The method of claim 57, wherein the second-polymer phasecomprises sites that are substantially or completely connectedthroughout the coating, such that elution of the drug from thesecond-polymer phase includes transport of the drug exclusively throughthe second-polymer phase.
 69. The method of claim 57, wherein the firstpolymer constitutes more in amount than the second polymer in thecomposition.
 70. The method of claim 57, wherein the forming comprises:blending the first polymer with the second polymer in the solvent toform a solution; and adding the drug to the solution such that the drugis preferentially incorporated in the second-polymer phase in thecoating.
 71. A drug-delivery stent comprising a coating, wherein thecoating includes: a first-polymer phase comprising a first-polymer, asecond-polymer phase comprising a second-polymer, and a drug; wherein,the second-polymer phase is partially or substantially phase-separatedfrom the first-polymer phase, and the drug is preferentiallyincorporated in the second-polymer phase.
 72. A method of coating astent comprising incorporating a drug preferentially in a second-polymerphase during a coating process, wherein the coating process comprises:forming a coating composition comprising a first polymer for afirst-polymer phase, a second polymer for a second-polymer phase, adrug, and a solvent; applying the composition to a stent; and removingthe solvent from the composition to form a coating with the drugpreferentially in the second-polymer phase, wherein the second-polymerphase is partially or substantially phase-separated from a first-polymerphase.
 73. A therapeutic composition for coating stents comprising: afirst polymer component; a second polymer component, wherein the secondpolymer component at least partially separates from the first polymercomponent when a coating is formed from the composition; and a drugbeing preferentially enriched in the second polymer component when thecoating is formed from the composition.
 74. The composition of claim 73,wherein the first-polymer component has a film forming property.
 75. Thecomposition of claim 73, wherein the drug comprises an antibiotic,antiproliferative, antineoplastic, anti-inflammatory, antiplatelet,anticoagulant, antifibrin, antithrombin, antimitotic, antioxidant, or acombination thereof.
 76. The composition of claim 73, wherein thecomposition forms second-polymer component sites that are substantiallyor completely disconnected when a coating is formed from thecomposition, such that elution of the drug from the coating occursthrough transport of the drug across both the second-polymer componentand the first-polymer component.
 77. The composition of claim 73,wherein the composition forms second-polymer component sites that aresubstantially or completely connected when a coating is formed from thecomposition, such that elution of the drug from the coating includestransport of the drug primarily through the second-polymer component.78. The composition of claim 73, wherein the composition formssecond-polymer component sites that are substantially or completelyconnected when a coating is formed from the composition, such thatelution of the drug from the coating includes transport of the drugexclusively through the second-polymer component.
 79. The composition ofclaim 73, wherein the concentration of the drug-enriched second-polymercomponent in the coating is less than or equal to about 30% by volume.80. The composition of claim 73, wherein the concentration of thedrug-enriched second-polymer component in the coating is greater than orequal to about 30% by volume.
 81. The composition of claim 73, whereinthe coating comprises the drug-enriched second-polymer component in aconcentration that is less than or equal to a percolation threshold ofthe coating.
 82. The composition of claim 73, wherein the coatingcomprises the drug-enriched second-polymer component in a concentrationthat is greater than or equal to a percolation threshold of the coating.83. The composition of claim 73, wherein the drug-enrichedsecond-polymer component has a glass-transition temperature of less thanabout 37° C.
 84. The composition of claim 73, wherein the drug has apreferential solubility for the second-polymer component, such that thedrug becomes preferentially incorporated in the second-polymer componentwhen the coating is formed from the composition.
 85. The composition ofclaim 73 additionally including a solvent used to form the coating, suchthat the drug has a preferential solubility in the solvent, and thesolvent preferentially solubilizes the second polymer over the firstpolymer, wherein the drug becomes preferentially incorporated in thesecond-polymer component upon removing the solvent to form the coating.